It has been known that eupatilin can be used as a therapeutic agent for treating inflammatory bowel diseases (see Korean Patent No. 0414453). Eupatilin is also known as a substance which inhibits the activity of farnesyl transferase, an enzyme essential for the activation of ras oncogenes and angiogenesis and therefore can be used as an inhibitor of oncogene expression, an anti-cancer agent, an inhibitor of cancer metastasis, and a prophylactic agent for diabetic retinopathy and angiogenesis-related blindness following keratoplasty (see Korean Patent Application Publication No. 2002-0090672 A1). Further, with respect to anticancer action, eupatilin is also known to suppress the activity, invasion and migration of matrix metalloproteinase (MMP) to thereby inhibit the progression and metastasis of breast cancer (Korean Patent Application Publication No. 2006-0121998 A1).
Meanwhile, estrogen, a hormone secreted by the ovary, refers to a steroid compound having a C18 estrane nucleus. Typically, there are well known 3 types of estrogen: estrone (E1), estradiol (E2), and estriol (E3). Estrogen is known to exert a wide variety of effects in numerous organs, in addition to modulation of menstrual cycles. For example, it regulates production of cholesterol in the liver, maintains the bone density in bone, and plays a role in maturation of uterine walls. In recent years, estrogen has also been found to play an important role in neuronal cell viability and adipogenesis.
When there is a decline of the body's estrogen level due to ovarian failure at the menopause period, this leads to a decrease in the blood estrogen level, which may result in common menopausal disorders including hot flashes, sweating, insomnia, depression and headache, and bone diseases due to a decreased bone density. Moreover, a decrease in the body's estrogen level brings about an increased risk of plaque formation in the vascular system, resulting in development of cardiovascular diseases such as atherosclerosis, an increased incidence of neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease caused by damage to the neuronal cells, and the occurrence of obesity resulting from deregulated adipogenesis (Deroo B J, Korach K S. (2006) “Estrogen receptors and human disease” J Clin Invest. Mar; 116(3):561-70.PMID: 16511588).
Although hormone therapies of administering animal-derived estrogens have been used for ameliorating menopausal disorders or the like due to such an estrogen level decline, it has been reported through the extensive randomized placebo-controlled study by the Women's Health Initiative (WHI) that such hormone therapies have potential side effects such as breast cancer, cardiovascular diseases, stroke, and blood clotting (Rossouw J E, Anderson G L, Prentice R L, et al. (2002). “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial”. JAMA 288 (3): 32133. PMID 12117397, Anderson G L, Limacher M, Assaf A R, et al. (2004). “Effects of conjugated equine estrogen in postmenopausal women with rhysterectomy: the Women's Health Initiative randomized controlled trial”. JAMA 291 (14): 170112. PMID 15082697).
To this end, there is a need for the development of a substance which exhibits little or no possibility of such side effects and exerts an estrogenic effect to thereby have therapeutic effects on bone diseases, menopausal disorders, cardiovascular diseases, neurodegenerative diseases and obesity resulting from estrogen deficiency.